Behavioral neurology is a subspecialty of neurology that studies the neurological basis of behavior, memory, and cognition, the impact of neurological damage and disease upon these functions, and the treatment thereof (see, e.g., Pincus and Tucker, Behavioral Neurology (2nd Edition), Oxford University Press, 1979). Neuropsychiatry is a closely related branch of medicine dealing with mood and mental disorders attributable to diseases of the nervous system (see, e.g., Price et al., Neurology (2000) 54:8-14). Both fields are involved in treating conditions which are associated with behavioral dysfunction in humans, such as mood disorders which include depression (e.g., Major Depressive Disorder), Bipolar Disorder, and Anxiety Disorder, and conditions characterized by atypical mood (e.g., depressed mood, irritability, instability of mood, and/or changes in mood), such as stress, hormonal mood swings (e.g., during pregnancy, during post-partum, during puberty, during menopause, or are a result of a Premenstrual Dysphoric Disorder or related condition), Mild Cognitive Impairment, substance-induced mood disorder (e.g., alcoholism), dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease, and psychotic disorders (e.g., Schizoaffective Disorder, Schizophrenia, Delusional Disorder, and Psychotic Disorder Not Otherwise Specified).
Major Depressive Disorder (MDD) is a neuropsychiatric condition which afflicts anywhere from 10 to 20% of the population. In the United States, MDD is a contributing cause to the majority of the approximately 30,000 annual deaths by suicide. It has additionally been speculated that some unknown proportion of the 100,000 deaths by other unnatural means such as motor vehicle accidents, homicide and workplace accidents are also related to underlying depressive symptoms. Such deaths are the sixth leading cause of mortality in the United States. Medical treatment of depression over the years has included the use of psychotherapy and prescription anti-depressants. While generally helpful, these drugs are limited in their efficacy by their innate toxicity as well as a significant tendency to unpleasant side effects, such as nausea, sexual dysfunction, cognitive slowing, emotional dulling, lethargy, and sleep disturbances, as well as potentially dangerous interactions with other medications. Moreover, in some instances the subject being treated is a non-responder to the prescription anti-depressant therapy. More recently, an association has been noted between the use of modern (e.g., more conventional) prescription anti-depressants and the emergence of suicidal ideation, which is observed in a previously non-suicidal population. This risk appears particularly prominent in younger patients, e.g., those under the age of 24. This has in turn led to resistance to the use of this class of medication in pediatric, adolescent, and post-adolescent populations. Somewhat ironically, such under-treatment may have been associated with a spike in suicide deaths in the under-19 population between 2003 and 2004.
It therefore remains of great interest to explore safer alternatives for treating neuropsychiatric conditions, especially conditions associated with atypical mood, such as depression, e.g., Major Depressive Disorder.